AIH for Spinal Cord Repair

NCT03780829 | Terminated Early Phase 1 DMC FDA Drug

• 1 other identifier: B2848-R
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Contusive cervical spinal cord injury (cSCI) impairs upper limb function (reach-and-grasp) which limits daily-life activities and thus decreases the quality of life. Promoting neuroplasticity may support upper limb recovery after SCI. Repetitive exposure to acute intermittent hypoxia (rAIH) combined with motor training promotes recovery of motor function after SCI; however, the overall effects of rAIH/training are limited. The investigators will use an adult rat model of long-term contusive cSCI to study novel approaches to enhance the effect of rAIH/training on forelimb function and study the neuronal substrate underlying the effects. The findings will be used to direct the development of more effective rAIH/training approaches for people with contusive, functionally incomplete, cSCI. Because deficits in upper limb function are a major problem after stroke, amyotrophic lateral sclerosis, multiple sclerosis, and other motor disorders, this work may also be relevant for patients with other types of central nervous system (CNS) lesions.

Conditions

SCI

Keywords

spinal cord injury; hypoxia; plasticity

Outcome Measures

Primary Outcomes (3)

• Change in grip strength

  Grip strength will be measured using a hand-held dynamometer, with an average force (measured in dynes) taken over the course of three trials. A rest break is provided between trials. Strength testing will be completed bilaterally.

  baseline, 1st week, 2nd week, 4th week, 8th week, and 12th week

• Change in pinch strength

  Pinch strength will be assessed using a digital pinch gauge (unit of Force= Newton). The minimum value of zero will be assigned when a participant cannot actively squeeze the pinch meter between the thumb and index finger. The mean value of total of 3 trials will be assessed, with a rest break provided between trials.

  baseline, 1st week, 2nd week, 4th week, 8th week, and 12th week

• Change in motor evoked potential size

  Resting and active motor thresholds (RMT and AMT) will be tested in each of the muscles using a stimulator.

  30 minutes before and 30 minutes after intervention

Study Arms (4)

hypoxia plus training

EXPERIMENTAL

combined hypoxia treatment with exercise training

Behavioral: hypoxia; Behavioral: exercise training

sham hypoxia plus training

SHAM COMPARATOR

combined sham hypoxia treatment with exercise training

Behavioral: sham hypoxia; Behavioral: exercise training

hypoxia plus training plus NMDA agonist

EXPERIMENTAL

combined hypoxia treatment with exercise training and with NMDA agonist treatment

Behavioral: hypoxia; Drug: D-cycloserine; Behavioral: exercise training

hypoxia plus training plus sham NMDA agonist

PLACEBO COMPARATOR

combined hypoxia treatment with exercise training and with sham NMDA agonist treatment

Behavioral: hypoxia; Drug: sham-NMDA agonist; Behavioral: exercise training

Interventions

hypoxia BEHAVIORAL

intermittent cycles of normoxia-hypoxia

hypoxia plus training; hypoxia plus training plus NMDA agonist; hypoxia plus training plus sham NMDA agonist

sham hypoxia BEHAVIORAL

intermittent cycles of sham hypoxia

sham hypoxia plus training

D-cycloserine DRUG

NMDA agonist treatment

Also known as: NMDA agonist

hypoxia plus training plus NMDA agonist

sham-NMDA agonist DRUG

sham-NMDA agonist treatment

hypoxia plus training plus sham NMDA agonist

exercise training BEHAVIORAL

bimanual massed practice training

hypoxia plus training; hypoxia plus training plus NMDA agonist; hypoxia plus training plus sham NMDA agonist; sham hypoxia plus training

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and females Veterans between 18-85 years
• Chronic cSCI (1 yr of injury)
• Cervical injury at C8 or above
• Sensory function: impaired (score of 1) but not absent (score of 0) or intact (score of 2) innervations in dermatomes C6, C7 and C8 during light touch and pin prick stimulus using the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) sensory scores
• Motor function: Able to grasp small objects with one hand and able to perform a visible precision grasp between the index finger and thumb
• Motor scores ISNCSCI: 1 to 4 but not 5 on finger flexors and finger abductors on the hand tested.
• These criteria were selected to ensure that hand impairment will not interfere with the ability to perform training and proposed tests
• Male and females (18-80 years)
• Right handed
• Able to complete precision and power grips

You may not qualify if:

• Uncontrolled medical problems including pulmonary, cardiovascular or orthopedic disease
• Any debilitating disease prior to the SCI that caused exercise intolerance
• Premorbid, ongoing major depression or psychosis, altered cognitive status
• History of head injury or stroke
• Metal plate in skull
• History of seizures
• Receiving drugs acting primarily on the central nervous system, which lower the seizure threshold such as antipsychotic drugs
• chlorpromazine
• clozapine
• or tricyclic antidepressants
• Pregnant females
• Ongoing cord compression or a syrinx in the spinal cord or who suffer from a spinal cord disease as spinal stenosis, spina bifida or herniated cervical disk
• resting heart rate \> 120 bpm
• resting systolic blood pressure \>180 mmHg
• resting diastolic blood pressure \>100 mmHg

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

Edward Hines Jr. VA Hospital, Hines, IL

Hines, Illinois, 60141-3030, United States

Location

MeSH Terms

Conditions

Spinal Cord Injuries; Hypoxia

Interventions

Cycloserine; Exercise

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oxazolidinones; Oxazoles; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Martin Oudega, PhD

  Edward Hines Jr. VA Hospital, Hines, IL

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: participants and some research personnel will be blinded
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: repetitive intermittent hypoxia treatment combined with exercise and/or NMDA agonist

Study Record Dates

• First Submitted: December 12, 2018
• First Posted: December 19, 2018
• Study Start: February 25, 2020
• Primary Completion: February 5, 2026
• Study Completion: February 5, 2026
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)